The interaction of SV40 large T antigen with unspecific double-stranded DNA: an electron microscopic study

Virology. 1992 Jul;189(1):293-303. doi: 10.1016/0042-6822(92)90705-t.

Abstract

T antigen, an early protein encoded by simian virus 40 (SV40), is a specific DNA-binding protein with high affinity for elements in the viral origin of replication where it forms a double-hexameric complex as a prerequisite for DNA untwisting and, in the presence of ATP hydrolysis, for DNA unwinding. Like other specific DNA-binding proteins, T antigen also associates with DNA strands of random sequence albeit at reduced affinity. In addition, T antigen is able to unwind unspecific DNA sequences starting from internal binding sites. This property could be a step in the pathway leading to the chromosomal rearrangements that are frequently observed in SV40-transformed cells. This possibility prompted us to investigate the binding of T antigen to unspecific DNA using electron microscopy. We observed that the protein binds randomly to many unspecific DNA sites excluding a preference for particular DNA sequences or structural features. Addition of ATP to the binding buffer induces the formation of oligomeric, possibly hexameric, T antigen complexes that frequently align to form long arrays of DNA-bound protein. Magnesium salts induce the formation of tightly packed T antigen aggregates which bind to DNA to form many DNA branches and loops that emanate from the aggregated protein core. Upon ATP hydrolysis, aggregated T antigen catalyzes the unwinding of DNA duplices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Antigens, Polyomavirus Transforming / drug effects
  • Antigens, Polyomavirus Transforming / metabolism
  • Antigens, Polyomavirus Transforming / ultrastructure*
  • Binding Sites
  • DNA, Viral / drug effects
  • DNA, Viral / metabolism
  • DNA, Viral / ultrastructure*
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / ultrastructure*
  • Histocytological Preparation Techniques
  • Microscopy, Electron
  • Sensitivity and Specificity

Substances

  • Antigens, Polyomavirus Transforming
  • DNA, Viral
  • DNA-Binding Proteins
  • adenosine 5'-O-(3-thiotriphosphate)
  • Adenosine Triphosphate